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MedicalResearch.com Interview with:
Dr Robert Boyle, Reader in Paediatric Allergy
Department of Medicine
Imperial College London

MedicalResearch.com: What is the background for this study?

Response: Diet in early life may influence whether or not an infant develops allergies or autoimmune disease. We undertook a project for the UK Food Standards Agency to evaluate the evidence for this.

MedicalResearch.com: What are the main findings?

Response: We found that a probiotic supplement during the last 2-4 weeks of pregnancy and during breastfeeding may reduce an infant’s chances of developing eczema; and that omega-3 fatty acid supplements taken from the middle of pregnancy (20 weeks gestation) through the first few months of breastfeeding may reduce an infant’s chances of developing food allergy. We also found links between longer duration of breastfeeding and improved infant health, but for most other variations in diet during pregnancy or infancy we did not find evidence for a link with allergies or autoimmune disease.

MedicalResearch.com Interview with:M.Victoria Moreno-ArribasSpanish National Research Council | CSIC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Recent discoveries indicate polyphenols might also promote health by actively interacting with bacteria in the gut. Also, the intake of specific polyphenol-rich beverages and foods helps the maintenance of digestive health and prevention of disease status. However, the knowledge of the effects of polyphenols in relation to the prevention of dental diseases is still at an early stage.

The use of antiseptics and/or antibiotics in the prevention and treatment of periodontal diseases can lead to unwanted effects. Therefore, there is a need to develop novel antimicrobial strategies useful for the prevention and management of these diseases. Oral epithelial cells normally constitute a physical barrier that prevents infections, but bacterial adhesion to host tissues constitutes a first key step in the infectious process.

With the final goal to elucidate the health properties of wine polyphenols at oral level, we studied their properties as an anti-adhesive therapy for periodontal and cariogenic prevention, as well as the combined action between wine polyphenols and oral probiotic strains in the management of microbial-derived oral diseases. In particular, we checked out the effect of two red wine polyphenols, as well as commercially available grape seed and red wine extracts, on bacteria that stick to teeth and gums and cause dental plaque, cavities and periodontal disease. Also, oral metabolism of polyphenols, including both oral microbiota and human mucosa cells, was investigated.Continue reading →

Response: We have shown in earlier observational studies that there is an association between probiotic intake and lower risk of preterm delivery and preeclampsia. Since pregnancy is a time of rapid change and different exposures can have different effect depending on the time of exposure, we wanted to find out if there is any special time point of consumption that might be of greater importance when it comes to these associations.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Infant colic is excessive crying in babies less than 3 months old with no underlying medical cause. It affects 1 in 5 newborns, is very distressing, and is associated with maternal depression, Shaken Baby Syndrome, and early cessation of breastfeeding. Up to now, there has been no single effective treatment for colic. The probiotic Lactobacillus reuteri DSM 17938 has recently shown promise but results from trials have been conflicting. In particular, a previous trial from Australia, the largest in the world so far, did not find the probiotic to be effective in both breastfed and formula-fed infants with colic.

This international collaborative study, which collected raw data from 345 infants from existing trials from Italy, Poland, Canada and Australia, confirms Lactobacillus reuteri to be effective in breastfed infants with colic. However, it cannot be recommended for formula-fed infants with colic.

Compared to a placebo, the probiotic group was two times more likely to reduce crying by 50 per cent, by the 21st day of treatment, for the babies who were exclusively breastfed. The number needed to treat for day 21 success in breastfed infants was 2.6.

In contrast, the formula fed infants in the probiotic group seemed to do worse than the placebo group, but the numbers for this group were limited.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previously, we found that people with schizophrenia and bipolar disorder had an increased susceptibility to Candida albicans yeast infections, which was sex specific and associated with memory deficits. Also in an earlier placebo-controlled probiotic study, we found that although probiotics improved the overall bowel function of people with schizophrenia, there was no effect by this treatment on psychiatric symptoms. Given that C. albicans infections can upset the dynamics of the human microbiome, we decided to re-evaluate the potential benefit of probiotics in the context of a patient’s C. albicans yeast status. Not only was bowel function again enhanced following intake of probiotics, but yeast antibody levels were decreased by this treatment.

Furthermore, psychiatric symptoms were actually improved over time for men receiving probiotics who did not have elevated C. albicansantibodies. Men who were positive for C. albicans exposure, however, consistently presented with worse psychiatric symptoms irrespective of probiotic or placebo treatment.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: A number of groups have demonstrated the ability of probiotics to benefit digestive health and there is a growing body of evidence to suggest an association between mental health and “gut health”. We were interested to see if probiotic bacteria could decrease anxiety- or stress-related behavior in a controlled setting using zebrafish as our model organism of choice for these studies.

We were able to show that Lactobacillus plantarum decreased overall anxiety-related behavior and protected against stress-induced dysbiosis (microbial imbalance). The fact that administration of probiotic bacteria also protected other resident gut bacteria from the dramatic changes seen in “stressed” fish not receiving the probiotic was unexpected and suggested that these bacteria may be working at the level of the GI tract and the central nervous system.

Response: Nephrolithiasis is the second most prevalent kidney disease in USA after hypertension, with a rising prevalence and complications including advanced chronic kidney disease (CKD) and end stage renal disease (ESRD). It remains a major source of patient discomfort and disability, lost working days, and health-care expenditure, with an annual economic cost approaching $10 billion. Hyperoxaluria is a major risk factor for kidney stones (KS), and 70-80% of KS are composed of calcium oxalate. Urinary oxalate is an important determinant of supersaturation, and the risk for stone formation is affected by small increases in urine oxalate. Oxalate is a metabolic end product that cannot be further metabolized and is highly toxic. The mammalian intestine plays a crucial role in oxalate homeostasis, by regulating the amount of absorbed dietary oxalate and providing an avenue for enteric oxalate excretion. Anion exchanger SLC26A6 (A6)-mediated intestinal oxalate secretion plays a critical role in preventing hyperoxaluria and calcium oxalate kidney stones (COKS). Inflammatory bowel disease patients have a significantly increased risk of kidney stones due to the associated enteric hyperoxaluria. Obesity is a risk factor for KS and obese stone formers often have mild to moderate hyperoxaluria. Hyperoxaluria is also emerging as a major complication (developing in > 50% of patients) of bariatric surgery for obesity. With the rising prevalence of obesity and increased utilization of bariatric surgery, it is expected that the incidence of hyperoxaluria and related COKS (including the associated cost burden) will continue to increase at a significant rate. Primary hyperoxaluria (PH) is an inherited disease in which there is endogenous oxalate overproduction, which leads to recurrent KS and/or progressive nephrocalcinosis, ESRD, as well as significant hyperoxalemia, systemic oxalosis and premature death. Systemic deposition of calcium oxalate (oxalosis) leads to bone disease, cardiac arrhythmias, cardiomyopathy, skin ulcers, erythropoietin refractory anemia, and digital gangrene. The only treatment known to fully correct the underlying metabolic defect is liver transplantation or combined kidney-liver transplantation once ESRD develops. In addition, significant hyperoxalemia is also seen in ESRD. Cardiovascular diseases are the leading cause of morbidity and mortality in ESRD patients, and a recent report raised the possibility that the ESRD-associated hyperoxalemia might contribute to this increased risk. Lowering serum oxalate might improve cardiovascular outcomes in ESRD patients if these findings are confirmed.

Unfortunately, there is currently no specific therapy that effectively lowers urine and/or plasma oxalate level(s), and the risk of recurrent COKS, nephrocalcinosis, oxalate nephropathy, ESRD, & systemic oxalosis remains substantial in the absence of treatment.

Dr. Shen: Clostridium difficile infection (CDI) is a persistent, healthcare associated infection with significant morbidity and mortality that costs the US billions of dollars annually. Prevention is imperative, particularly for patients at high risk for infection – hospitalized adults taking antibiotics. Trials have suggested probiotics may be useful in preventing CDI. We conducted a systematic review with meta-analysis in this high-risk population, hospitalized adults receiving antibiotics, to evaluate the current evidence for probiotic use for prevention of CDI.

Medical Research: What is the background for this study? What are the main findings?

Dr. Uusitalo: The TEDDY Study is an international prospective cohort study with the primary goal to identify environmental causes of Type 1 Diabetes (T1D). It is carried out in six clinical research centers, in four countries: University of Colorado Health Science Center (US), Georgia Regents University (US), Pacific Northwest Diabetes Research Institute (US), Turku University Hospital (Finland), Institute of Diabetes Research (Germany), and Lund University (Sweden), since 2004.

One possible environmental factor related to Type 1 Diabetes etiology is diet. Dietary supplements including probiotics as well as various types of infant formulas including probiotic fortified infant formula are studied. The microbial composition of gut has been shown to be associated with the development of Type 1 Diabetes. Colonization of the infant gut starts already in utero and early microbial exposures have been found to be important in defining the trajectory of colonization. Probiotics have been demonstrated to induce favorable immunomodulation and it has been suggested that probiotic treatment could prevent T1D. Therefore we wanted to study the early exposures of probiotic and risk of islet autoimmunity, a condition often preceding Type 1 Diabetes.

This study produced very interesting results. The main finding was that we found 60% decrease in the risk of islet autoimmunity among children with HLA genotype of DR3/4 (high risk), who were exposed to probiotics during the first 27 days of life.

Medical Research: What is the background for this study? What are the main findings?

Response: Food supplements, among which probiotics, are becoming more and more popular. A lot is known about the effect of probiotics on the physical functioning, but even though there are some rat studies on the effects of probiotics on mental well-being, not much is known about the effect in humans. The few studies on humans that are available show beneficial effects on mood when people experience a bad mood, or psychological distress. Worldwide, millions of people are suffering from mood disorders like for instance depression, but not everyone receives treatment for this. Probiotics are safe and easily available, and we therefore wanted to investigate if probiotics could perhaps be promising in serving as a preventive or adjuvant therapy for mood disorders of anxiety or depression. We therefore focused on cognitive reactivity to sad mood, which measures the degree to which people activate dysfunctional thought patterns when experiencing a sad mood. This measure is known to be predictive of the onset and development of depression. Compared to subjects who received a 4-week placebo intervention, participants who received a 4-week multispecies probiotics intervention showed significantly reduced aggressive and ruminative thoughts. Even if preliminary, these results provide the first evidence that the intake of probiotics may help reduce negative thoughts associated with sad mood. As such, our findings shed an interesting new light on the potential of probiotics to serve as adjuvant or preventive therapy for depression.

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